The goal of these investigations is to understand the factors which control the folding of immunoglobulin subunits and their assembly into functional antibodies. The specific protein studied is a human myeloma IgG1 immunoglobulin. In vitro pathways of covalent assembly, identification of intermediates and the kinetics of conversion of each intermediate on the pathway will be examined, at various pH values, temperatures and electrolyte concentrations. The influence of L chains on rates of disulfide formation between H chains, and of H chains on rates of formation of the H-L half molecule will be investigated by oxidations of separated H chains in the presence and absence of L chains, and by oxidation of HL half molecules, in the absence of free H or L chains, respectively. The influence of domain interactions on folding and assembly will be studied by examining rates and pathways of non-covalent and covalent assembly using separated C and V region peptides, and mixtures of the peptides in recombination studies. Various spectral methods will be employed as probes of conformation of the separated and recombined fragments, intermediates and wholly assembled molecules. Comparison of reconstituted and native myeloma protein molecules will be made by immunochemical techniques. BIBLIOGRAPHIC REFERENCES: Mollie N. Pflumm and Sherman Beychok. Alkali and Urea Induced Conformation Changes in Concanavalin A. Biochemistry, 13 4982 (1974). Duane W. Sears, Jonathan Mohrer and Sherman Beychok. A Kinetic Study In Vitro of the Reoxidation of Interchain Disulfide Bonds in a Human IgGlk. Correlation Between Sulfhydryl Disappearance and H2L2 Assembly intermediates. Proc. Natl. Acad. Sci., U.S., 72: 353-357 (1975).